Effects of Malaria Heme Products on Red Blood Cell Deformability

Forradee Nuchsongsin Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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Kesinee Chotivanich Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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Prakaykaew Charunwatthana Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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Omodeo-Salè Fausta Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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Donatella Taramelli Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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Nicholas P. Day Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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Nicholas J. White Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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Arjen M. Dondorp Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand; Institute of General Physiology and Biochemistry, University of Milan, Milan, Italy; Department of Public Health–Microbiology–Virology, University of Milan, Milan, Italy; Centre for Tropical Medicine, Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford United Kingdom

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In falciparum malaria, the deformability of the entire erythrocyte population is reduced in proportion to disease severity, and this compromises microcirculatory blood flow through vessels partially obstructed by cytoadherent parasitized erythrocytes. The cause of rigidity of uninfected erythrocytes in not known but could be mediated by malaria heme products. In this study, we show that red blood cell deformability (RBC-D), measured by laser-assisted optical rotational cell analyzer, decreased in a dose-dependent manner after incubation with hemin and hydrogen peroxide but not with hemoglobin or β-hematin. Hemin also reduced mean red cell volume. Albumin decreased and N-acetylcysteine (NAC) both prevented and reversed rigidity induced by hemin. Hemin-induced oxidative damage of the membrane seems to be a more important contributor to pathology than cell shrinkage because the antioxidant NAC restored RBC-D but not red blood cell volume. The findings suggest novel approaches to the treatment of potentially lethal malaria.

Author Notes

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